Ryotaro Kamohara

Pharmacokinetics of repeated dosing of linezolid in a hemodialysis patient with chronic renal failure.

Linezolid (LZD) is thought not to require dose adjustment in patients with renal dysfunction, making it a drug of choice for these patients. However, in the current study we show LZD accumulation occurring with repeated dosing during hemodialysis in a 64-year-old man receiving hemodialysis treatment. In this patient, methicillin-resistant Staphylococcus aureus (MRSA) caused an abscess under the abdominal wall due to wound infection after colon cancer surgery. Treatment was initiated with intravenous LZD (600 mg) every 12 h. However, pancytopenia and liver dysfunction occurred during the LZD administration period. A high trough level, of 15–20 μg/ml, during LZD administration was determined from stored blood biochemistry samples, and pharmacokinetic parameters, estimated by the Bayesian nonlinear least squares method, were as follows: clearance (CL), 1.56 l/h; clearance during hemodialysis (CLHD), 2.23 l/h; volume of distribution (Vd), 18.69 l; and area under the curve (AUC), 384.07 μg/ml · h. Simulation of the serum concentration-time profile from the estimated pharmacokinetic parameters gave a trough level about four to five times higher than that in healthy individuals in the early administration period, indicating LZD accumulation in blood. These findings suggest a causal relationship between the high LZD level and the adverse effects. The cause of the high LZD level is unclear, but the findings indicate that careful monitoring and dose adjustment of LZD is necessary in hemodialysis patients.

Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells

Bioengineered lungs consisting of a decellularized lung scaffold that is repopulated with a patient’s own cells could provide desperately needed donor organs in the future. This approach has been tested in rats, and has been partially explored in porcine and human lungs. However, existing bioengineered lungs are fragile, in part because of their immature vascular structure. Herein, we report the application of adipose-derived stem/stromal cells (ASCs) for engineering the pulmonary vasculature in a decellularized rat lung scaffold. We found that pre-seeded ASCs differentiated into pericytes and stabilized the endothelial cell (EC) monolayer in nascent pulmonary vessels, thereby contributing to EC survival in the regenerated lungs. The ASC-mediated stabilization of the ECs clearly reduced vascular permeability and suppressed alveolar hemorrhage in an orthotopic transplant model for up to 3 h after extubation. Fibroblast growth factor 9, a mesenchyme-targeting growth factor, enhanced ASC differentiation into pericytes but overstimulated their proliferation, causing a partial obstruction of the vasculature in the regenerated lung. ASCs may therefore provide a promising cell source for vascular regeneration in bioengineered lungs, though additional work is needed to optimize the growth factor or hormone milieu for organ culture.

Intratracheal Administration of Recombinant Human Keratinocyte Growth Factor Promotes Alveolar Epithelial Cell Proliferation during Compensatory Lung Growth in Rat

Keratinocyte growth factor (KGF) is considered to be one of the most important mitogens for lung epithelial cells. The objectives of this study were to confirm the effectiveness of intratracheal injection of recombinant human KGF (rhKGF) during compensatory lung growth and to optimize the instillation protocol. Here, trilobectomy in adult rat was performed, followed by intratracheal rhKGF instillation with low (0.4 mg/kg) and high (4 mg/kg) doses at various time-points. The proliferation of alveolar cells was assessed by the immunostaining for proliferating cell nuclear antigen (PCNA) in the residual lung. We also investigated other immunohistochemical parameters such as KGF, KGF receptor and surfactant protein A as well as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Consequently, intratracheal single injection of rhKGF in high dose group significantly increased PCNA labeling index (LI) of alveolar cells in the remaining lung. Surprisingly, there was no difference in PCNA LI between low and high doses of rhKGF with daily injection, and PCNA LI reached a plateau level with 2 days-consecutive administration (about 60%). Our results indicate that even at low dose, daily intratracheal injection is effective to maintain high proliferative states during the early phase of compensatory lung growth.

Adenocarcinoma arising from an enteric cyst of the posterior mediastinum

Mediastinal enteric cysts are rare congenital thoracic cysts. The majority of mediastinal enteric cysts occur in infants, while they are rare in adults. Although most of these cysts are benign, surgical resection is sometimes performed, and malignant changes found in enteric cysts are rare. A 52-year-old man was incidentally discovered to have a posterior mediastinal mass and we excised the mass thoracoscopically. Histopathological findings showed an enteric cyst with adenocarcinoma. Comparing the pathological and magnetic resonance imaging (MRI) findings, MRI would help to detect malignant changes in such cysts. Although malignant changes found in mediastinal enteric cysts are extremely rare, clinicians should always keep in mind that those cysts have malignant potential and careful evaluation of MRI would be a clue for surgical indication.

Double stenting with silicone and metallic stents for malignant airway stenosis

For severe malignant airway stenosis, there are several types of commercially available airway stents, and each has its own advantages and disadvantages. We herein describe the safety and efficacy of combination stenting with silicone and metallic stents for patients with extended malignant airway stenosis. Seven patients with malignant airway stenosis were treated via combination stenting with a silicone stent and a metallic stent for extended airway stenosis from the central to peripheral airways. Five patients were diagnosed with advanced esophageal cancer, two of whom had tracheoesophageal fistulas. One patient had adenoid cystic carcinoma, and another had mediastinal tumor. There were no specific complications related to the double stenting. Combination stenting with silicone and metallic stents proved to be a safe option for patients with severe, extended, and complicated malignant airway stenosis.

Temporary bypass for superior vena cava reconstruction with Anthron bypass tube TM

Total superior vena cava (SVC) clamping for SVC replacement or repair can be used in thoracic surgery. A bypass technique is an option to avoid hemodynamic instability and cerebral venous hypertension and hypoperfusion. The present report describes a venous bypass technique using Anthron bypass tubeTM for total SVC clamping. Indications for this procedure include the need for a temporary bypass between the brachiocephalic vein and atrium for complete tumor resection. This procedure allows the surgeons sufficient time to complete replacement of SVC or partial resection of SVC without adverse effects. Further, it is a relatively simple procedure requiring minimal time.

Single lung retrieval from a donor supported by a left ventricular assist device

The number of patients who need cardiac support with a left ventricular assist device (LVAD) has increased over the last decade. However, the number of reports of organ retrieval from donors with an LVAD is still small. Successful lung retrieval for single lung transplantation was performed from a donor on LVAD support. This required special care not to injure the heart, great vessels, and the device, particularly the outflow conduit, because of significant conglutination around the device. A right single lung transplantation was performed successfully, with no postoperative complications. This means that patients on an LVAD could be potential donors for lung transplantation.

Avoiding completion pneumonectomy by omentopexy for bronchial dehiscence

A 56-year-old man underwent right upper sleeve lobectomy with mediastinal lymph node dissection after induction chemoradiotherapy (CRT) for advanced non-small cell lung cancer (NSCLC). The patient developed anastomotic dehiscence 11 days postoperatively. A fistula measuring 10 mm in diameter was found around the transition region between cartilage and membranous portions of the bronchus. To avoid completion right pneumonectomy, omentopexy was performed to cover the bronchial dehiscence and facilitate healing. The patients condition improved after a redo operation with surveillance bronchoscopy to check the anastomotic status. Omentopexy may be a feasible treatment option for bronchial dehiscence and could help to avoid completion pneumonectomy (CP).

Is early postoperative administration of pregabalin beneficial for patients with lung cancer?—randomized control trial

BACKGROUND Post-thoracotomy pain is an obstacle for lung-cancer patients even after introduction of less invasive surgical procedures. The aim of this prospective study was to evaluate if early postoperative administration of pregabalin is beneficial for patients with non-small cell lung cancer (NSCLC). METHODS We conducted a randomized open control trial. Patients with NSCLC were allocated randomly to epidural and nonsteroidal anti-inflammatory drug (NSAID) use for analgesia (control group) or pregabalin use (pregabalin group). Primary endpoint was the frequency of additional administration of a NSAID. Secondary endpoints were intensity of ongoing pain, frequency of neuropathic pain, and pain catastrophizing. RESULTS Seventy-two patients were registered and allocated. Thirty-four cases in the control group and 33 in the pregabalin group were assessed. Age, sex, body mass index (BMI), type of surgical procedure, type of lymph-node dissection, operation time, bleeding, duration of chest-tube insertion, and postoperative hospital stay between the two groups was not significantly different. Frequency of additional NSAID use between the control group (2±4 suppositories) and pregabalin group (2±3 suppositories) was not significantly different (P=0.62). Numeric Rating Scale (NRS) for the intensity of ongoing pain, frequency of neuropathic pain, and Pain Catastrophizing Scale (PCS) between each group were not significantly different at any time until 3 months after surgery. CONCLUSIONS Early postoperative administration of pregabalin is not beneficial for patients with NSCLC.

Overexpression of the adiponectin gene mimics the metabolic and stress resistance effects of calorie restriction, but not the anti-tumor effect

Adiponectin (Adipoq), a peptide hormone secreted from the white adipose tissue, may play a role in the anti-aging and/or anti-tumor effects of calorie restriction (CR). We analyzed metabolic traits in Adipoq gene-overexpressing mice fed ad libitum with a regular diet (RD) or a high-fat diet (HFD), or fed 30% CR of RD initiated at 12 weeks of age. Adipoq-RD and -HFD mice at 6 months of age showed reduced blood glucose and insulin concentrations, and thus increased insulin sensitivity, compared with WT mice fed a RD or a HFD. In the epididymal white adipose tissue in Adipoq mice, senescence-like changes such as upregulation of p53 protein and of biomarkers of inflammation, Cd68 and Ccl2 mRNA, were ameliorated compared with WT-RD and WT-HFD mouse tissues. Resistance to stress induced by lipopolysaccharide was also strengthened in Adipoq mice compared with WT mice. These metabolic changes and stress resistance were also noted in the WT-CR mice, suggesting that Adipoq plays a part in the effect of CR. In contrast, in an allograft tumor growth model, tumor growth was not inhibited in Adipoq mice. The present findings suggest that Adipoq plays a part in the anti-aging, but not in the anti-tumor, effects of CR.